Abstract

The fundamental premise underlying this proposal is that the normal program of differentiation in the adult mammalian myocardium changes in response to age and that these changes contribute to age-related differences in susceptibility to hypoxia and ischemia. Our major hypotheses are that the integration of the metabolic pathways for ATP synthesis and utilization changes during aging and, as a consequence, aged myocardium is more susceptible to acute hypoxic and ischemic injury. Corollary hypotheses are (1) that these changes are similar to those observed in chronic hypoxia and many forms of hypertrophy, (23) that decreased energy reserve (the CK system) contributes to increased susceptibility and (3) that changes in glycolytic capacity of the aged myocardium contribute to differences in pHi regulation during hypoxia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG010829-04
Application #
6295601
Study Section
Project Start
1996-07-01
Project End
1999-06-30
Budget Start
Budget End
Support Year
4
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Zhang, X; Azhar, G; Nagano, K et al. (2001) Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts. J Am Coll Cardiol 38:2055-62
Levy, B R; Hausdorff, J M; Hencke, R et al. (2000) Reducing cardiovascular stress with positive self-stereotypes of aging. J Gerontol B Psychol Sci Soc Sci 55:P205-13
Azhar, G; Liu, L; Zhang, X et al. (1999) Influence of age on hypoxia/reoxygenation-induced DNA fragmentation and bcl-2, bcl-xl, bax and fas in the rat heart and brain. Mech Ageing Dev 112:5-25
Azhar, G; Gao, W; Liu, L et al. (1999) Ischemia-reperfusion in the adult mouse heart influence of age. Exp Gerontol 34:699-714
Spindler, M; Saupe, K W; Tian, R et al. (1999) Altered creatine kinase enzyme kinetics in diabetic cardiomyopathy. A(31)P NMR magnetization transfer study of the intact beating rat heart. J Mol Cell Cardiol 31:2175-89
Vijg, J (1999) Genetics of aging. Sponsored by Cold Spring Harbor Laboratory, 2-5 April 1998. Biochim Biophys Acta 1423:R1-12
Khrapko, K; Bodyak, N; Thilly, W G et al. (1999) Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions. Nucleic Acids Res 27:2434-41
van Orsouw, N J; Zhang, X; Wei, J Y et al. (1998) Mutational scanning of mitochondrial DNA by two-dimensional electrophoresis. Genomics 52:27-36
Liu, L; Azhar, G; Gao, W et al. (1998) Bcl-2 and Bax expression in adult rat hearts after coronary occlusion: age-associated differences. Am J Physiol 275:R315-22
Turner, N A; Xia, F; Azhar, G et al. (1998) Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J Mol Cell Cardiol 30:1789-801

Showing the most recent 10 out of 23 publications